METABOLISME PROTEIN DAN ASAM AMINO

Evi Umayah Ulfa

TOPIK BAHASAN

Pencernaanprotein danpenyerapanasam amino

Siklus UreaBiosintesis

Asam Amino Non Esensial

MetabolismeNukleotida

Proteins and Amino Acids

• Essential – must be consumed in the diet

• Nonessential – can be synthesized in the body

Source of Amino Acids

Amino Acid Absorption

• Amino acids are absorbed in the small intestine

• Amino acids are transported to the liver from the intestines via the portal vein

• In the liver, amino acids are

– Used to synthesize new proteins

– Converted to energy, glucose, or fat

– Released to the bloodstream and transported to cells throughout the body

• Occasionally proteins are absorbed intact

Amino acid Catabolism

• Amino acids cannot be stored.

• If there is an excess of amino acids or a lack of other energy sources, the body will use them for energy production.

Amino acid degradation requires the removal of the amino group as ammonium.

• Ammonium must then be disposed of as it is toxic to the body.

How Much Protein?

• A 70 kg person (154 lb) typically consumes 100 g protein per day (dietary protein)

• To stay in nitrogen balance that person must excrete 100 g of N products per day

• The body makes 400 g of protein per day and 400 g are broken down into amino acids (body protein)

• 300 g of amino acids recycled into new protein, 100 g are degraded (urea cycle, glucose, ketone bodies)

• Total protein = 500 g/day, 400 g degraded, 400 resynthesized and 100 g catabolized

NITROGEN BALANCE

Nitrogen balance = nitrogen ingested - nitrogen excreted

(primarily as protein) (primarily as urea)

Nitrogen balance = 0 (nitrogen equilibrium)

protein synthesis = protein degradation

Positive nitrogen balance

protein synthesis > protein degradation

Negative nitrogen balance

protein synthesis < protein degradation

Nitrogen Balance and Imbalance

Figure 6.12

Dietary Protein…Digestion

Proteolytic Enzymes

Penyerapan AsamAmino

• Transpor aktif sekunder(dependen Na)

• Difusi terfasilitasi

• Siklus glutamil

Kotranspor Na dan Asam Amino

• Transport asam amino transepitel

• Lumen ke Vena portamelalui sel epitel

• Transporter : symporter– Na dan asam amino– Na dikeluarkan dari sel

epitel melalui transport aktifsedangkan asam amino masuk ke pembuluh darah(vena porta) melalui difusiterfasilitasi

Siklus Glutamil

Degradation of Body Protein (existing protein within the cells)

• All protein within the cells have the half life

( t1/2)

• Hemoglobin, muscle proteins, digestive enzymes, and the proteins of cells sloughed off from the gastrointestinal tract Extensive Synthesis and Degradation

• Two Mechanism :– lysosomes

– the ubiquitin/proteasome system

Protein Degradation

Ubiquitin/Proteasome Pathway

80-90%

Most intracellular proteins

• Lysosomal processes

10-20%

Extracellular proteins

Cell organelles

Some intracellular proteins

LYSOSOMES

Digestive System of the Cell

• Digests– ingested materials

– obsolete cell components

• Degrades macromolecules of all types– Proteins

– Nucleic acids

– Carbohydrates

– Lipids

• Heterogeneous

Lysosomal Enzymes

• 50 different degradative enzymes

• Acid hydrolases– Active at pH 5

(inside lysosome)– Inactive if released

into cytosol (pH 7.2)

• Acidic pH of lysosomes maintained by a proton

pump in the lysosomal membrane– Requires ATP, thus mitochondria

Different pathways lead to the lysosome1) Phagocytosis–Cell “eating” of material

> 250nm

2) Pinocytosis–Cell “drinking”

< 150nm

3) Receptor Mediated Endocytosis

-clathrin-coated pits

4) Autophagy–“self eat” of old worn out organelles, – important in cell degradation during apoptosis

Protein degradation in the lysosomes

Lysosomes degrade extracellular proteins that the cell incorporates by endocytosis.

Lysosomes can also degrade intracellular proteins that are enclosed in other membrane-limited organellas.

In well-nourished cells, lysosomal protein degradation is non-selective (non-regulated).

In starved cells, lysosomes degrade preferentially proteins containing a KFERQ “signal” peptide.

The regression of the uterus after childbirth is mediated largely by lysosomal protein degradation

The Ubiquitin/Proteasome

PATHWAY

UBIQUITIN

K

G

Small peptide that is a “TAG”

76 amino acids

C-terminal glycine - isopeptide

bond with the e-amino group of

lysine residues on the substrate

Attached as monoubiquitin or

polyubiquitin chains

Three genes in humans:

Two are stress genes (B and C)

One, UbA as a fusion protein

The 26S proteasome

Ubiquitinated proteins are degraded by the proteasome

Proteasomal protein degradation consumes ATP.

The proteasome degrades the proteins to ~8 amino-acid

peptides.

Access of proteins into the proteasome is tightly regulated.

The peptides resulting from the proteasome activity diffuse

out of the proteasome freely.

Ubiquitinated proteins are degraded in the cytoplasm and

nucleus by the proteasome.

The Ubiquitin/Proteasome Pathway

Four Main Steps:

UBIQUITINATION

RECOGNITION

DEGRADATION

DEUBIQUITINATION

NEURODEGENERATION

associated with

Alzheimer’s DiseaseParkinson’s Disease

Huntington’s DiseaseAmyotrophic Lateral Sclerosis

Parkinson’s Disease

Alzheimer’s Disease

Huntington’s Disease

Amyotrophic lateral

sclerosis

Spinocerebellar Ataxia

Disease

accumulation of

misfolded

proteins

Cell

Death

Neurodegenerative Disorders

Ubiquitin-Protein Aggregates

HUNTINGTON’S ALZHEIMER’S

PARKINSON’S LOU GEHRIG’S

f

PD: ubiquitin

c

AD: tau

d

AD: ubiquitin